Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways.

BACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers. METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data. RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium. CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.

Specificity in the processing of a subject's own name.

Subject's own name (SON) is widely used in both daily life and the clinic. Event-related potential (ERP)-based studies have previously detected several ERP components related to SON processing; however, as most of these studies used SON as a deviant stimulus, it was not possible to determine whether these components were SON-specific. To identify SON-specific ERP components, we adopted a passive listening task with EEG data recording involving 25 subjects. The auditory stimuli were a SON, a friend's name (FN), an unfamiliar name (UN) selected from other subjects' names and seven different unfamiliar names (DUNs). The experimental settings included Equal-probabilistic, Frequent-SON, Frequent-FN and Frequent-UN conditions. The results showed that SON consistently evoked a frontocentral SON-related negativity (SRN) within 210-350 ms under all conditions, which was not detected with the other names. Meanwhile, a late positive potential evoked by SON was found to be affected by stimulus probability, showing no significant difference between the SON and the other names in the Frequent-SON condition, or between the SON and a FN in the Frequent-UN condition. Taken together, our findings indicated that the SRN was a SON-specific ERP component, suggesting that distinct neural mechanism underly the processing of a SON.

Electroacupuncture Stimulation Suppresses Postoperative Inflammatory Response and Hippocampal Neuronal Injury.

Postoperative cognitive dysfunction (POCD) is consequence of anesthesia and surgery that primarily affects older people. The prevention and treatment of POCD has drawn an increasing attention in recent decades. Here, we established the animal model mimicked POCD after femoral fracture surgery, and analyze the effect of acupuncture stimulation on postoperative cognitive function after femoral fracture surgery. Compared with the mock group, the cognitive function performance was significantly decreased both in the anaesthesia group and the surgery group, between which the symptoms were more severe in the surgery group. The peripheral inflammation response and the neuron impairment and inflammation response in the hippocampus were observed in the surgery group, but only peripheral inflammation response was detected in the anaesthesia group. These findings indicated the POCD was the synergistic outcome of anaesthesia and surgical stimulation but with different pathogenic mechanism. The surgery with mental tri-needles (surgery+MTN) group outperformed the surgery group in terms of cognitive function performance. The peripheral inflammation response and the neuron impairment and inflammation response in the hippocampus was significantly reduced by the electroacupuncture stimulation. Our findings indicated the protection of electroacupuncture form POCD after femoral fracture surgery is related to the inhibition of inflammation response and neuron impairment.

Linezolid Consumption Facilitates the Development of Linezolid Resistance in Enterococcus faecalis in a Tertiary-Care Hospital: A 5-Year Surveillance Study.

Although case reports and clinical studies of linezolid (LZD)-resistant Enterococcus faecalis (LREF) have gradually increased in recent years, the relationship between LZD resistance and antibiotic consumption in hospital settings still remains unclear. In this study, we aimed to investigate the dynamic relationship between the yearly detection frequency of LREF clinical isolates and yearly consumption of LZD and vancomycin (VCM) over a 5-year period in a Chinese hospital setting. Antibiotic consumption data (LZD and VCM) from 2011 to 2015 were obtained from a computerized database and recalculated as the defined daily doses (DDDs) per 100 bed-days (DBD). All 268 E. faecalis clinical isolates were retrospectively collected from 2011 to 2015 in this hospital. LZD resistance mechanism and multilocus sequence typing of E. faecalis were determined by PCR. The annual detection frequency of LREF clinical isolates tested in this hospital was shown with 1.89% (1/53), 2% (1/50), 2.04% (1/49), 0% (0/45), and 7.04% (5/71), respectively, and the detection frequency of LZD-nonsusceptible E. faecalis (LNSEF; n = 59, including LZD-resistant and intermediate isolates) was determined with 26.42% (14/53), 34% (17/50), 16.33% (8/49), 22.22% (10/45), and 14.08% (10/71), respectively. Spearman correlation analysis revealed that LZD DBD significantly correlated positively with the detection frequency of LREF (r = 0.886, p = 0.019). Moreover, VCM DBD significantly correlated positively with the frequency of LNSEF (r = 0.943, p = 0.005). Furthermore, the detection frequency of optrA-positive E. faecalis also correlated positively with high LZD consumption load in this hospital setting. Conclusively, high LZD consumption load facilitates the development of LZD resistance and promotes the selection of optrA-positive E. faecalis clinical isolates under antibiotic pressure in a hospital setting.

The initial deficiency of protein processing and flavonoids biosynthesis were the main mechanisms for the male sterility induced by SX-1 in Brassica napus.

BACKGROUND: Rapeseed (Brassica napus) is an important oil seed crop in the Brassicaceae family. Chemical induced male sterility (CIMS) is one of the widely used method to produce the hybrids in B. napus. Identification of the key genes and pathways that involved in CIMS were important to understand the underlying molecular mechanism. In the present report, a multi-omics integrative analysis, including of the proteomic, transcriptomic and miRNAs, combined with morphological and physiological analysis were conducted. RESULTS: Earlier degeneration of the tapetosomes and elaioplasts, aberrantly stacking in tapetal cells and incompletely deposition in tryphine of pollen wall were observed in chemical hybridization agent (CHA) of SX-1 treated B. napus through SEM and TEM analysis. It was revealed that the deficiencies in protein processing in endoplasmic reticulum (ER) and flavonoids biosynthesis were occurred at early stage in the SX-1 treated materials. Subsequently, plant hormone signal transduction, biosynthesis of amino acids, fatty acids and steroid in anther at later stages were identified down-regulated after SX-1 treatment. 144 transcript factors (TFs) were also indentified to down-regulated at early stage, which suggested the early regulation in anther and pollen wall development were disordered in CHA treated B. napus. In addition, 7 important miRNAs were identified and 2 of the predicted target genes of miRNAs were Rf-like genes. CONCLUSIONS: Taken together, an interaction network of candidate genes and the putative metabolism pathways were constructed based on the multi-omics integrative analysis, it provided a new insight into the male sterility induced by CHA of SX-1 in B. napus.

Screening Estrogen Receptor Modulators in a Paper-Based Breast Cancer Model.

The health risks associated with acute and prolonged exposure to estrogen receptor (ER) modulators has led to a concerted effort to identify and prioritize potential disruptors present in the environment. ER agonists and antagonists are identified with end-point assays, quantifying changes in cellular proliferation or gene transactivation in monolayers of estrogen receptor alpha expressing (ER+) cells upon exposure. While these monolayer cultures can be prepared, dosed, and analyzed in a highly parallelized manner, they are unable to predict the potencies of ER modulators in vivo accurately. Physiologically relevant model systems that better predict tissue- or organ-level responses are needed. To address this need, we describe here a screening platform capable of quantitatively assessing ER modulators in 96 chemically isolated 3D cultures. These cultures are supported in wax-patterned paper scaffolds whose design has improved performance and throughput over previously described paper-based setups. To highlight the potential of paper-based cultures for toxicity screens, we measured the potency of known ER modulators with a luciferase-based reporter assay. We also quantified the proliferation and invasion of two ER+ cell lines in the presence of estradiol. Despite the inability of the current setup to better predict in vivo potencies of ER modulators than monolayer cultures, the results demonstrate the potential of this platform to support increasingly complex and physiologically relevant tissue-like structures for environmental chemical risk assessment.

Near-Infrared Light-Activatable Microneedle System for Treating Superficial Tumors by Combination of Chemotherapy and Photothermal Therapy.

Because of the aggressive and recurrent nature of cancers, repeated and multimodal treatments are often necessary. Traditional cancer therapies have a risk of serious toxicity and side effects. Hence, it is crucial to develop an alternative treatment modality that is minimally invasive, effectively treats cancers with low toxicity, and can be repeated as required. We developed a light-activatable microneedle (MN) system that can repeatedly and simultaneously provide photothermal therapy and chemotherapy to superficial tumors and exert synergistic anticancer effects. This system consists of embeddable polycaprolactone MNs containing a photosensitive nanomaterial (lanthanum hexaboride) and an anticancer drug (doxorubicin; DOX), and a dissolvable poly(vinyl alcohol)/polyvinylpyrrolidone supporting array patch. Because of this supporting array, the MNs can be completely inserted into the skin and embedded within the target tissue for locoregional cancer treatment. When exposed to near-infrared light, the embedded MN array uniformly heats the target tissue to induce a large thermal ablation area and then melts at 50 °C to release DOX in a broad area, thus destroying tumors. This light-activated heating and releasing behavior can be precisely controlled and switched on and off on demand for several cycles. We demonstrated that the MN-mediated synergistic therapy completely eradicated 4T1 tumors within 1 week after a single application of the MN and three cycles of laser treatment. No tumor recurrence and no significant body weight loss of mice were observed. Thus, the developed light-activatable MN with a unique embeddable feature offers an effective, user-friendly, and low-toxicity option for patients requiring long-term and multiple cancer treatments.

Cleavage of phosphorus-carbon (P-C) bonds of α-amino phosphonates with intramolecular hydrogen migration in the gas phase using electrospray ionization tandem mass spectrometry.

RATIONALE: α-Amino phosphonates with intrinsic biological activities have been used in a wide variety of applications. Because of the widespread existence of natural organophosphorus compounds containing P-C bonds such as the α-amino phosphonates, it is important to investigate the gas-phase chemistry of P-C bonds in order to determine their basic properties, which might provide some insights into their biosynthesis and catalytic cleavage. METHODS: Twenty α-amino phosphonates were successfully synthesized and their fragmentation behavior was systematically investigated using in-solution deuterium labeling in combination with high-resolution Fourier transform ion cyclotron resonance (FTICR) electrospray ionization tandem mass spectrometry. RESULTS: The fragmentation pathways of twenty α-amino phosphonates with different chemical structures were systematically studied. In general, P-C bonds could be easily cleaved via a novel intramolecular hydrogen atom migration from the amino group to the phosphoryl group through a five-membered-ring intermediate in the gas phase. A possible mechanism of the rearrangement of α-amino phosphonates is proposed. CONCLUSIONS: An interesting intramolecular hydrogen atom migration between the amino and phosphoryl groups was observed with cleavage of the P-C bond in the molecule through a five-membered-ring intermediate. This characteristic fragmentation pathway not only provides some insights into the basic chemistry of compounds with P-C bonds, but could also have some applications in the structural determination of the α-amino phosphonate analogues.

Proteomic and comparative genomic analysis of two Brassica napus lines differing in oil content.

Ultrastructural observations, combined with proteomic and comparative genomic analyses, were applied to interpret the differences in protein composition and oil-body characteristics of mature seed of two Brassica napus lines with high and low oil contents of 55.19% and 36.49%, respectively. The results showed that oil bodies were arranged much closer in the high than in the low oil content line, and differences in cell size and thickness of cell walls were also observed. There were 119 and 32 differentially expressed proteins (DEPs) of total and oil-body proteins identified. The 119 DEPs of total protein were mainly involved in the oil-related, dehydration-related, storage and defense/disease, and some of these may be related to oil formation. The DEPs involved with dehydration-related were both detected in total and oil-body proteins for high and low oil lines and may be correlated with the number and size of oil bodies in the different lines. Some genes that corresponded to DEPs were confirmed by quantitative trait loci (QTL) mapping analysis for oil content. The results revealed that some candidate genes deduced from DEPs were located in the confidence intervals of QTL for oil content. Finally, the function of one gene that coded storage protein was verified by using a collection of Arabidopsis lines that can conditionally express the full length cDNA from developing seeds of B. napus.

[Investigation on the rate of bone fracture of primary osteoporosis treated by embedding thread at Shenshu (BL 23) during five years].

OBJECTIVE: To observe the clinical effect of embedding thread at Shenshu (BL 23) for preventing and treating primary osteoporosis. METHODS: Seventy cases, who had been treated in 2001-2003 at our hospital, were selected and the bone mineral density (BMD) before and after treatment and the incidence condition of bone fracture during 5 years after treatment were analyzed in the embedding thread group and the medication group. RESULTS: The BMDs of hip and lumbar vertebrae were both increased in the embedding thread group, and the BMDs of femoral neck and femoral trochanter in this group were significantly higher than those in the medication group (both P < 0.05). The rate of bone fracture during 5 years after treatment was 2.1% (1/48) in the embedding thread group, which was significantly lower than 18.2% (4/22) in the medication group (P < 0 05). CONCLUSION: Embedding thread at Shenshu (BL 23) can raise the BMD of primary osteoporosis and significantly reduce the rate of bone fracture during 5 years.

[Effect of embedding thread at Shenshu (BL 23) on clinical pain of postmenopausal osteoporosis].

OBJECTIVE: To explore the effect of embedding thread at Shenshu (BL 23) on clinical pain of postmenopausal osteoporosis. METHODS: Fifty-six cases were randomly divided into an embedding thread group, an embedding thread plus Leli group and a Leli group. The pain of the patient before treatment, 3 months and 6 months after treatment were assessed. RESULTS: There was significant difference before and after treatment in the score of pain in both the embedding thread group and the embedding thread plus Leli group (P < 0.001), with no significant difference between the two groups (P > 0.05); there was no significant difference before and after treatment in the score of pain in the Leli group (P > 0.05), but with significant differences as compared with other two groups (both P < 0.001). CONCLUSION: Embedding thread at Shenshu (BL 23) has very obvious therapeutic effect on clinical pain of postmenopausal osteoporosis, and oral administration of Leli capsule has no significantly therapeutic effect on clinical pain of postmenopausal osteoporosis.